Work in this laboratory has helped to stimulate research into the development of ruthenium-containing anticancer agents in several laboratories world wide. Various types of ruthenium complexes are now under investigations as chemotherapeutic, radio-diagnostic or radio- sensitizing pharmaceuticals. Since both ruthenium-containing chemotherapeutic and radiosensitizing agents have DNA as their target molecule, a broad understanding of the interactions of simple ruthenium compounds with DNA and it's constituents are necessary to the development of these new types of pharmaceuticals. In our laboratory we have uncovered several new types of reactions involving both Ru(II) and Ru(III). Of particular interest are terpsichorean movements (controlled rotamerizations and linkage isomerizations that may be coupled) of the metal ion on individual bases, which can be choreographed by manipulating the solution pH and electrochemical potential. Preliminary results with recently developed electrochemical techniques indicate that these metal ion movements occur on DNA and are probably orchestrable. We plan to investigate several types of terpsichorean molecules and apply some to electrode surfaces to develop coatings with a high affinity for DNA that can be switched on and off. Owing to the strong pi-donor property or Ru(II) and pi-acceptor ability of Ru(III), chemical effects on nucleoside ligands are often observed with these ions prior to other systems. For example, the coordination of Ru(III) on the N7 site of purine nucleosides and nucleotides facilitates electron transfer to molecular oxygen and formation of a keto group at 4C8. This reaction should also occur on DNA and will be investigated as a potential method of selectively cleaving nucleic acids. Paramagnetic shifts in the NMR induced by the unpaired electron on Ru(III) make it easier to resolve otherwise closely spaced proton resonances and determine not only the binding site of the metal ion, but also possibly the conformation of the sugar moiety. We now plan to extend these studies to tRNA and oligonucleotides to illustrate this approach in determining the effect of coordinated metal ions on nucleic acid conformations. Ammine complexes of Os(II and III), the third row congener of Ru, exhibit rapid linkage isomerizations dependent on metal oxidation state, that should have analogs in the chemistry of nucleosides and nucleic acids. Mechanistic work with Tc(V), which is widely used in radiodiagnostic agents in nuclear medicine, now makes it possible to prepare stable complexes between oxo-Tc(V) will be prepared in an endeavor to extend the realm of terpsichorean movements on this type of ligand and devise new radiodiagnostic agents.